TYROSINE PHOSPHORYLATION OF P38 BUT NOT EXTRACELLULAR SIGNAL-REGULATED KINASE IN NORMAL HUMAN NEUTROPHILS STIMULATED BY TUMOR-NECROSIS-FACTOR - COMPARATIVE-STUDY WITH GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

We investigated the cytokine-specific involvement of two members of th e microtubule-associated protein kinase family, extracellular signal-r egulated kinase (ERK)(1 and 2) and p38, in normal human neutrophils. B oth tumor necrosis factor (TNF) and granulocyte-macrophage colony-stim ulating factor (GM-CSF) induced tyrosine phosphorylation of a 42-kDa p rotein in human neutrophils, though the time course of its phosphoryla tion and its band pattern in electrophoresis differed for each of the cytokines, In addition, GM-CSF, but not TNF, induced a mobility shift of 42-kDa ERK2 in human neutrophils, By using immunoprecipitation foll owed by immunoblotting, we clarified that GM-CSF, but not TNF, induced tyrosine phosphorylation of ERK2 and that TNF, but not GM-CSF, induce d tyrosine phosphorylation of p38, Results of a combined stimulation s tudy showed that tyrosine phosphorylation of ERK2 and that of p38 do n ot interfere or interact with each other at least in human neutrophils . These results indicate cytokine specific involvement and an independ ent activating system of ERK and p38 in normal human neutrophils stimu lated by two cytokines which share many biological activities in these cells. (C) 1997 Academic Press.